posted on 2024-01-18, 13:08authored byTorsten John, Aldo Rampioni, David Poger, Alan E. Mark
The
self-assembly of peptides and proteins into β-sheet rich
amyloid fibrils is linked to both functional and pathological states.
In this study, the growth of fibrillar structures of the short peptide
GNNQQNY, a fragment from the yeast prion Sup35 protein, was examined.
Molecular dynamics simulations were used to study alternative mechanisms
of fibril growth, including elongation through binding of monomers
as well as fibril self-assembly into larger, more mature structures.
It was found that after binding, monomers diffused along preformed
fibrils toward the ends, supporting the mechanism of fibril growth
via elongation. Lateral assembly of protofibrils was found to occur
readily, suggesting that this could be the key to transitioning from
isolated fibrils to mature multilayer structures. Overall, the work
provides mechanistic insights into the competitive pathways that govern
amyloid fibril growth.